Prostaglandin derivatives

ABSTRACT

Prostaglandin compounds substituted at the 11-position, and possessing bronchodilating and hypotensive activity are prepared from PGA 2  and its esters and 15-epimers.

This is a division of U.S. application Ser. No. 384,769, filed Aug. 1,1973, now U.S. Pat. No. 3,845,042; which in turn is acontinuation-in-part of U.S. application Ser. No. 282,200, filed Aug.21, 1972, and now abandoned.

BACKGROUND OF THE INVENTION

The prostaglandins are a group of hormone-like substances which may beviewed as derivatives of prostanoic acid. Several prostaglandins arefound widely distributed in mammalian tissue and have been isolated fromthis source. These prostaglandins have been shown to possess a varietyof biological properties such as bronchodilation, the ability to reducegastric secretion, to modify muscle tone, as well as the ability toraise or lower blood pressure.

The present invention concerns prostaglandin compounds in which the11-position (using the prostanoic acid numbering system) is variouslysubstituted with chemical groupings not found in nature.

SUMMARY OF THE INVENTION

The invention sought to be patented in a first composition aspectresides in the concept of a chemical compound of the structure ##STR1##wherein R¹ is nitromethyl, vinyl, phenyl, methyl, benzyl, cyano,mercapto, (lower)alkylthio, phenylthio, carboxycyanomethyl,carb(lower)alkoxycyanomethyl, dicarboxymethyl,dicarb(lower)-alkoxymethyl, dicyanomethyl, or carbamoylcyanomethyl; R²is hydroxy, tetrahydropyranyloxy, or acetoxy; and R³ is hydrogen or(lower)alkyl.

The tangible embodiments of the first composition aspect of theinvention possess the inherent general physical properties of beingclear to yellow oils, are substantially insoluble in water and aregenerally soluble in organic solvents such as ethyl acetate and ether.Examination of compounds produced according to the hereinafter describedprocess reveals, upon infrared, nuclear magnetic resonance, and massspectrographic analysis, spectral data supporting the molecularstructures herein set forth. The aforementioned physicalcharacteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the first composition aspect of theinvention possess the inherent applied use characteristic of exertingbronchodilating and hypotensive effects upon administration towarm-blooded animals as evidenced by pharmacological evaluationaccording to standard test procedures, and, in addition, are useful asintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in a second composition aspectresides in the concept of a chemical compound of the structure ##STR2##wherein R¹ is cyano, carboxy, carbamoyl, formyl, hydroxymethyl, acetyl,1-hydroxethyl, or nitromethyl; R² is hydroxy or acetoxy, and R³ ishydrogen or lower alkyl.

The tangible embodiments of the second composition aspect of theinvention possess the inherent general physical properties of beingeither crystalline solids or clear to yellow oils, are substantiallyinsoluble in water and are generally soluble in polar solvents such asethyl acetate and ether. Examination of compounds produced according tothe hereinafter described process reveals, upon infrared, nuclearmagnetic resonance, and mass spectrographic analysis, spectral datasupporting the molecular structures herein set forth. The aforementionedphysical characteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the second composition aspect of theinvention possess the inherent applied use characteristic of exertingbronchodilating and hypotensive effects upon administration towarm-blooded animals as evidenced by pharmacological evaluationaccording to standard test procedures, and, in addition, are useful asintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in a third composition aspectresides in the concept of a chemical compound of the structure ##STR3##wherein R¹ is carboxy, acetyl, carbamoyl, hydroxymethyl, or1-hydroxyethyl.

The tangible embodiments of the third composition aspect of theinvention possess the inherent general physical properties of beingclear to yellow oils, are substantially insoluble in water and aregenerally soluble in polar solvents such as ethyl acetate and ether.Examination of compounds produced according to the hereinafter describedprocess reveals, upon infrared, nuclear magnetic resonance, and massspectrographic analysis, spectral data supporting the molecularstructures herein set forth. The aforementioned physicalcharacteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the third composition aspect of theinvention possess the inherent applied use characteristic of exertingbronchodilating and hypotensive effects upon administration towarm-blooded animals as evidenced by pharmacological evaluationaccording to standard test procedures, and, in addition, are useful asintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in a fourth composition aspectresides in the concept of a chemical compound of the structure ##STR4##wherein R¹ is nitromethyl or cyano.

The tangible embodiments of the fourth composition aspect of theinvention possess the inherent general physical properties of beingeither crystalline solids or clear to yellow oils, are substantiallyinsoluble in water and are generally soluble in polar solvents such asethyl acetate and ether. Examination of compounds produced according tothe hereinafter described process reveals, upon infrared, nuclearmagnetic resonance, and mass spectrographic analysis, spectral datasupporting the molecular structures herein set forth. The aforementionedphysical characteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the fourth composition aspect of theinvention possess the inherent applied use characteristic of beingintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in a fifth composition aspectresides in the concept of a chemical compound of the structure ##STR5##wherein R¹ is nitromethyl or cyano and R² is methyl or phenyl. Thetangible embodiments of the fifth composition aspect of the inventionpossess the inherent general physical properties of being clear toyellow oils, are substantially insoluble in water and are generallysoluble in polar solvents such as ethyl acetate and ether. Examinationof compounds produced according to the hereinafter described processreveals, upon infrared, nuclear magnetic resonance, and massspectrographic analysis, spectral data supporting the molecularstructures herein set forth. The aforementioned physicalcharacteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the fifth composition aspect of theinvention possess the inherent applied use characteristic of beingintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in a sixth composition aspectresides in the concept of a chemical compound of the formula ##STR6##wherein R¹ is nitromethyl or cyano and R² is methyl or phenyl.

The tangible embodiments of the sixth composition aspect of theinvention possess the inherent general physical properties of beingclear to yellow oils, are substantially insoluble in water and aregenerally soluble in polar solvents such as ethyl acetate and ether.Examination of compounds produced according to the hereinafter describedprocess reveals, upon infrared, nuclear magnetic resonance, and massspectrographic analysis, spectral data supporting the molecularstructures herein set forth. The aforementioned physicalcharacteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the sixth composition aspect of theinvention possess the inherent applied use characteristic of exertingbronchodilating and hypotensive effects upon administration towarm-blooded animals as evidenced by pharmacological evaluationaccording to standard test procedures, and, in addition, are useful asintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in a seventh composition aspectresides in the concept of a chemical compound of the formula ##STR7##wherein R¹ is nitromethyl or cyano and R² is methyl or phenyl.

The tangible embodiments of the seventh composition aspect of theinvention possess the inherent general physical properties of beingclear to yellow oils, are substantially insoluble in water and aregenerally soluble in polar solvents such as ethyl acetate and ether.Examination of compounds produced according to the hereinafter describedprocess reveals, upon infrared, nuclear magnetic resonance, and massspectrographic analysis, spectral data supporting the molecularstructures herein set forth. The aforementioned physicalcharacteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the seventh composition aspect of theinvention possess the inherent applied use characteristic of exertingbronchodilating and hypotensive effects upon administration towarm-blooded animals as evidenced by pharmacological evaluationaccording to standard test procedures, and, in addition, are useful asintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in an eighth composition aspectresides in the concept of a chemical compound of the formula ##STR8##wherein R¹ is carbamoyl, methyl, carboxy, benzyl, nitromethyl, phenyl,cyano, carb(lower)alkoxycyanomethyl, carboxycyanomethyl,dicarb(lower)alkoxymethyl, dicarboxymethyl, hydroxymethyl, acetyl, or1-hydroxyethyl; R² is hydroxy, tetrahydropyranyloxy or acetoxy; and R³is hydrogen or (lower)alkyl.

The tangible embodiments of the eighth composition aspect of theinvention possess the inherent general physical properties of beingclear to yellow oils, are substantially insoluble in water and aregenerally soluble in polar solvents such as ethyl acetate and ether.Examination of compounds produced according to the hereinafter describedprocess reveals, upon infrared, nuclear magnetic resonance, and massspectrographic analysis, spectral data supporting the molecularstructures herein set forth. The aforementioned physicalcharacteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the eighth composition aspect of theinvention possess the inherent applied use characteristic of exertingbronchodilating and hypotensive effects upon administration towarm-blooded animals as evidenced by pharmacological evaluationaccording to standard test procedures, and, in addition, are useful asintermediates in the synthesis of other compositions of the invention.

The invention sought to be patented in a ninth composition aspect of theinvention relates in the concept of a chemical compound of the formula##STR9## wherein R¹ is mercapto, nitromethyl, vinyl, phenyl, methyl,phenyl, benzyl, cyano, (lower)alkylthio, phenylthio, carboxycyanomethyl,dicarboxymethyl, dicyanomethyl, or carbamoylcyanomethyl; R² is hydroxyor tetrahydropyranyloxy; and R³ is hydrogen or (lower)alkyl.

The tangible embodiments of the ninth composition aspect of theinvention possess the inherent general physical properties of beingclear to yellow oils, are substantially insoluble in water and aregenerally soluble in polar solvents such as ethyl acetate and ether.Examination of compounds produced according to the hereinafter describedprocess reveals, upon infrared, nuclear magnetic resonance, and massspectrographic analysis, spectral data supporting the molecularstructures herein set forth. The aforementioned physicalcharacteristics, taken together with the nature of the startingmaterials, the mode of synthesis, and the elemental analyses, confirmthe structure of the compositions sought to be patented.

The tangible embodiments of the ninth composition aspect of theinvention possess the inherent applied use characteristic of exertingbronchodilating and hypotensive effects upon administration towarm-blooded animals as evidenced by pharmacological evaluationaccording to standard test procedures, and, in addition, are thesynthesis of other compositions of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In describing the synthesis of the compositions of the invention,reference will be made to the following figure wherein the formulaerepresenting the various aspects of the invention are assigned Romannumerals for purposes of identification. The numerals assigned are thesame as those indicated above in the Summary of the Invention, and thedefinitions of R¹, R², and R³ are the same as those which were denotedfor each corresponding aspect.

The starting materials of formula I are either known compounds or simplederivatives thereof readily prepared by means known to those skilled inthe art of chemistry. Thus the starting materials 15-epiprostaglandin-A₂and its methyl ester, acetate, may be isolated from Plexaura homomallaas described by Weinheimer and Spraggins, Tetrahedron Letters, 59, 5185(1969); prostaglandin-A₂ (Prostaglandins, Bergstrom et al., ed.,Interscience Publishers, 1967), and prostaglandin-A₂, methyl ester(Bundy et al., Annals of the N.Y. Academy of Sciences, 180, 76 1971!)and also known in the art. Starting materials where R² istetrahydropyranyloxy may be readily prepared by, for example, reactingthe corresponding 15-hydroxy starting material with dihydropyran in thepresence of p-toluenesulfonic acid, and prostaglandin-A₂, methyl ester,acetate, may be prepared from prostaglandin-A₂, methyl ester by, forexample, treatment with acetic anhydride in the presence of pyridine.

Compounds of formula II are prepared from the starting materials (I) by1,4-conjugate addition to the αβ-unsaturated ketone system. Thisaddition is accomplished either by treatment with Grignard eagents inthe presence of a cuprous compound, such as cuprous chloride, or bytreatment with a Michael reaction donor in the presence of a strongbase, or by treatment with a thiolating agent such as sodium sulfide,thiophenol, or ethanethiol. Where the compounds of formula II containester or ether groups, these may be hydrolyzed to afford thecorresponding free hydroxy-acid compounds. ##STR10##

Compounds of formula III are produced by treatment of the correspondingformula II compounds with a hydride reducing agent such as sodiumborohydride. The compounds of formula IV are produced by hydrogenationof the corresponding formula II or formula VI compounds, for example, byhydrogenation in the presence of palladium on carbon.

Ketal compounds of formula V are prepared by ketalization byart-recognized methods, such as treatment with ethylene glycol in thepresence of p-toluenesulfonic acid. Where the formula V compounds areesters, they may be hydrolyzed, for example, with methanolic sodiumhydroxide to afford the corresponding free hydroxy-acids. Compounds offormula V wherein R¹ is carbamoyl or carboxyl are prepared byhydrolyzing compounds V wherein R¹ is cyano, for example, by hydrolysiswith aqueous methanolic sodium hydroxide at reflux temperature followedby separation of the two products, for example, by silicachromatography. Compound V wherein R¹ is hydroxy-methyl is produced bytreating V wherein R¹ is cyano with triethoxyhydride followed by aqueoushydrolysis, preferably acidic, to give V where R¹ is formyl, followed byreduction, for example, with sodium borohydride. Compound V where R¹ isacetyl is prepared by treatment of V wherein R¹ is cyano with methylmagnesium bromide followed by aqueous acid. The acetyl compound may bereduced, for example, with sodium borohydride, to produce V wherein R¹is 1-hydroxyethyl.

Compounds of formula VI are prepared by deketalization by art-recognizedmethods of compounds of formula V, for example, by treatment withhydrochloric acid in tetrahydrofuran. The 15-ketone compounds of formulaVII are prepared by oxidation of compounds of formula V with Jonesreagent. Compounds of formula VIII are prepared by reaction of formulaVII compounds with methyl or phenyl Grignard reagent. Compounds offormula IX are prepared by deketalization of compounds of formula VIII,for example, with hydrochloric acid or perchloric acid intetrahydrofuran. Compounds of formula X are produced by hydrogenation ofcompounds of formula IX, for example, by hydrogenation in the presenceof palladium on carbon.

It will be apparent to those skilled in the art of chemistry that thecarbon atoms to which substituents R¹ and R² are attached in thecompositions of the invention are asymmetric carbon atoms, and as aconsequence these positions can be either of two epimericconfigurations. The symbol where used in this specification is toindicate that both possible configurations at each particular positionis intended and is included within the scope of the invention.Substituents R¹ are introduced in the preparation of the compounds ofthe invention, and their introduction results in the formation of amixture of the two epimeric forms with reference to that position. Incompounds of formulae VIII, IX, and X, substituents R² are similarlyintroduced at a previously non-asymmetric center, and again bothpossible configurations are formed in mixture. In the other compounds ofthe invention, the 15-position (to which R² is attached) is asymmetricin the starting material and remains so through the formation of thedesired product; as a result, the configuration at this position in theproduct will depend on the configuration in the starting material.Where, in the invention, epimeric mixtures are formed, they can, ifdesired, be separated by various means well-known in the art, such aschromatography.

Various compounds of the invention bear hydroxyl or carboxyl groupswhich can be readily esterified by art-recognized means to producesimple esters thereof; similarly, various compounds bear carboxyl groupsand can be readily converted to their alkali metal salts or a salt of apharmacologically acceptable cation derived from ammonia or a basicamine. All such esters and salts are full equivalents of the subjectmatter particularly claimed.

Where used in this specification and claims, the terms "(lower)alkyl"and "(lower)alk-" include straight and branched chain hydrocarbonradicals of from 1 to about 6 carbon atoms.

In using the compounds of the invention to produce brochodilatingeffects in warm-blooded animals, they may be administered in a varietyof dosage forms: oral, injectable, and oral inhalation. Oral inhalationadministration is a preferred route because of its rapid onset ofaction, great potency, and specificity of action. The particular dosageto obtain the bronchodilating effect will vary with the particularcompound employed, the particular animal involved, and the degree ofbronchodilation desired. In the guniea pig, by the oral inhalationroute, the dose to produce bronchodilation is from about 0.2 microgramsto about 100 micrograms, and preferably from about 5 to about 50micrograms. The bronchodilation produced upon oral inhalationadministration can be observed by the method of Rosenthale et al., Int.Arch. Pharmacol., 172, 91 (1968).

In the use of the compounds of the invention to produce hypotensiveeffects in warm-blooded animals, administration by the injectable routeis preferred, preferably the intravenous route.

The following examples further illustrate the best mode contemplated bythe inventors of making the compositions of the invention.

EXAMPLE 1 7-2-(3-S-Hydroxy-1-Octenyl)-5-Oxo-3-Cyclopenten-1-Yl!-5-Heptenoic Acid,Methyl Ester

A solution of 16.0 g. of PGA₂ in 200 ml. of ether was treated withexcess diazomethane in ether and kept at 25° for 1 hour. The excessdiazomethane was decomposed with acetic acid and the mixture dilutedwith ether, washed with water and dried over sodium sulfate. Evaporationof the solvent gave 17.0 g. of the title product as an oil, λ_(max)^(film) 3.0, 3.45, 5.75, 5.85 μ.

EXAMPLE 2 7- 2-(3-S-Tetrahyropyran-2-Yloxy!-1-Octenyl)-5-Oxo-3-Cyclopenten-1-Yl!-5-HeptenoicAcid

A solution of 10.0 g. of PGA₂, 4.0 g. of dihydropyran and 0.06 g. ofp-toluenesulfonic acid in 300 ml. of benzene was stirred at 25° for onehour. The reaction mixture was diluted with ether, washed with water anddried over sodium sulfate. Evaporation and silica chromatography of theresidue with 30% ethyl acetate in hexane gave 4.4 g. of the titleproduct as an oil, λ_(max) ^(film) 3.45, 5.85, 6.3, 9.8, 10.3 μ; λ_(max)^(95%) EtOH 218 mμ (ε 9,600).

EXAMPLE 3 7- 2-(3-S-Tetrahydropyran-2-Yloxy!-1-Octenyl)-5-Oxo-3-Cyclopenten-1-Yl!-5-HeptenoicAcid, Methyl Ester

A solution of 1.0 g. of 7- 2-(3-S-tetrahydropyran-2-yloxy!-1-octenyl)-5-oxo-3-cyclopenten-1-yl!-5-heptenoicacid in 20 ml. of ether was treated with excess diazomethane in etherand the mixture kept at 25° for 0.5 hours. After destroying the excessdiazomethane with acetic acid, the solution was washed with water anddried over sodium sulfate. Evaporation of the solvent gave 0.95 g. ofthe title product as an oil, λ_(max) ^(film) 3.45, 5.8, 5.9, 9.7, 10.3μ; λ_(max) ^(95%) EtOH 218 mμ (ε 9,600). NMR: δ 7.55 (dd, J=1.5, 6.0,11--H), 6.20 (dd, J=2.2, 6.0, 10--H), 5.50 (M, 4, olefinic), 4.68 (M, 1,O--CH--O), 3.68 (s, 3, OCH₃) ppm. Mass spectrum: M⁺ at m/e 432 (theory432), M⁺ --OCH₃ at m/e 401.2746 (theory 401.2690).

EXAMPLE 4 7- 2-(3-R-Tetrahydropyran-2-Yloxy!-1-Octenyl)-5-Oxo-3-Cyclopenten-1-Yl!-5-Heptenoic Acid

A solution of 3.936 g. of 15-epi-PGA₂ and 1.5 g. of dihydropyran in 100ml. of benzene was treated with 25 mg. of p-toluenesulfonic acid and themixture stirred at 25° under nitrogen for 1 hour. The reaction mixturewas diluted with ether, washed with water and dried over sodium sulfate.The solvent was evaporated and the residue chromatographed on silica andeluted with 30% ethyl acetate in hexane to obtain 3.75 g. of the titleproduct as an oil, λ_(max) ^(film) 3.4, 5.8, 6.3, 9.8, 10.25 μ; λ_(max)^(95%) EtOH 219 mμ (ε 9,800). NMR: δ 7.55 (dd, J=2.2, 6.0, 11-H), 6.25(dd, J=1.5, 6.0, 10-H), 5.48 (M, 4, olefinic), 4.72 (bs, 1, O--CH--O)ppm. Mass spectrum: M⁺ --OPy at m/e 317.2099 (theory 317.2116).

EXAMPLE 5 7- 2-(3-S-Hydroxy-1-Octenyl)-5-Oxo-3-Cyclopenten-1-YL!-5-Heptenoic Acid, Methyl Ester,Acetate

A solution of 17.0 g. of 7-2-(3-S-hydroxy-1-octenyl)-5-oxo-3-cyclopenten-1-yl!-5-heptenoic acid,methyl ester, in 300 ml. of pyridine and 30 ml. of acetic anhydride wasstirred at 25° for 6 hours. The reaction mixture was concentrated undervacuum, diluted with ether, washed with water and dried over sodiumsulfate. Evaporation of the solvent and silica chromatography of theresidue with 15% ethyl acetate in hexane gave 15.3 g. of the titleproduct as an oil, λ_(max) ^(film) 3.45, 5.7, 5.8, 6.3, 8.0, 9.25, 10.25μ.

EXAMPLE 6 7-2-(3-R-Hydroxy-1-Octenyl)-3-Nitromethyl-5-Oxocyclopentyl!-5-HeptenoicAcid, Methyl Ester, Acetate

A solution of 13.4 g. of 15-epi-PGA₂, methyl ester, acetate and 37.3 ml.of nitromethane in 250 ml. of methanol was treated with 1.485 g. ofsodium methylate and the mixture stirred at 25° under nitrogen for 2hours. The reaction mixture was diluted with ether, washed with waterand dried over sodium sulfate. Evaporation and chromatography of theresidue on silica with 40% ethyl acetate in hexane gave 8.9 g. of thetitle product as an oil, λ_(max) ^(film) 3.4, 5.7, 6.4, 8.0, 9.8, 10.3μ. NMR: δ 5.60 (M, 2, 13 and 14-H), 5.37 (M, 3, 5-6-15-H), 4.45 (M, 2,CH₂ NO₂), 3.67 (S, 3, OCH₃), 2.06 (s, acetate) ppm.

EXAMPLE 7 7-2-(3-R-Hydroxy-1-Octenyl)-3-Nitromethyl-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 0.60 g. of 7-2-(3-R-hydroxy-1-octenyl)-3-nitromethyl-5-oxocyclopentyl!-5-heptenoicacid, methyl ester, acetate in 20 ml. of methanol was treated with 15ml. of 1N sodium hydroxide and the mixture stirred at 25° under nitrogenfor 0.5 hours. The reaction mixture was added to water, acidified withhydrochloric acid and extracted with ether. After washing with water anddrying over sodium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 30% ethyl acetate in hexane gave0.653 g. of the title product as an oil, λ_(max) ^(film) 3.0 (shoulder),3.4, 5.7, 5.8, 6.4, 7.2, 10.3 μ. NMR: δ 6.70 (s, 2, OH), 5.60 (M, 2, 13and 14-H), 5.40 (M, 2, 5 and 6-H), 4.45 (M, 2, CH₂ NO₂), 4.15 (M, 1,15-H) ppm. Mass spectrum: M⁺ at m/e 395 (theory 395), M⁺ --H₂ O at m/e377.2224 (theory 377.2201).

EXAMPLE 8 7- 2-(3-R- Tetrahydropyran-2-Yloxy!-1-Octenyl)-5-Oxo-3-Vinylcyclopentyl!-5-Heptenoic Acid

A solution of 5.75 ml. of 3.35 M vinyl magnesium chloride in 15 ml. ofTHF was added dropwise to an ice-cooled mixture of 0.65 g. of 7- 2-(3-R-tetrahydropyran-2-yloxy!-1-octenyl)-5-oxo-3-cyclopenten-1-yl!-5-heptenoicacid and 1.27 g. of cuprous chloride in 25 ml. of THF with stirringunder nitrogen. After stirring at 0° for 1 hour, the reaction mixturewas added to aqueous ammonium chloride solution and extracted withether. After washing with water and drying over sodium sulfate, theextract was evaporated and the residue chromatographed on silica.Elution with 20% ethyl acetate in hexane gave 0.27 g. of the titleproduct as an oil, λ_(max) ^(film) 3.45, 5.75, 5.85, 6.1, 9.8, 10.25,11.0 μ. NMR: δ 4.7-5.7 (M, 7, olefinic), 4.75 (bs, O--CH--O) ppm. Massspectrum: M⁺ --OPy at m/e 345.2433 (theory 345.2429).

EXAMPLE 9 7-2-(3-R-Hydroxy-1-Octenyl)-5-Oxo-3-Vinylcyclopentyl!-5-Heptenoic Acid

An ice-cooled solution of 0.30 g. of 7- 2-(3-R-tetrahydropyran-2-yloxy!-1-octenyl)-5-oxo-3-vinylcyclopentyl!-5-heptenoicacid in 20 ml. of THF was treated with 5.0 ml. of hydrochloric acid andthe mixture stirred at 0° under nitrogen for 5 minutes. The reactionmixture was diluted with water, extracted with ether and the extractwashed with water and dried over sodium sulfate. Evaporation and silicachromatography of the residue with 30% ethyl acetate in hexane gave 0.13g. of the title product as an oil, λ_(max) ^(film) 3.0, 3.45, 5.8, 6.1,10.3, 10.95 μ. NMR: δ -4.8-5.9 (M, 7, olefinic), 4.2 (M, 1, 15-H) ppm.Mass spectrum: M⁺ at m/e 362 (theory 362).

EXAMPLE 10 7-2-(3-R-Hydroxy-1-Octenyl)-5-Oxo-3-Phenylcyclopentyl!-5-Heptenoic Acid

A solution of 3.84 ml. of 2.5M phenyl magnesium chloride in 15 ml. ofTHF was added dropwise to an ice-cooled mixture of 0.62 g. of 7- 2-(3-R-tetrahydropyran-2-yloxy!-1-octenyl)-5-oxo-3-cyclopenten-1-yl!-5-heptenoicacid and 0.61 g. of cuprous chloride in 20 ml. of THF and stirred undernitrogen at 0° C. for 0.5 hours. The reaction mixture was added toaqueous ammonium chloride solution and extracted with ether. Afterwashing with water and drying over sodium sulfate, the extract wasevaporated and the residue chromatographed on silica. Elution with 20%ethyl acetate in hexane afforded 0.26 g. of an oil which was dissolvedin 25 ml. of 20% hydrochloric acid in THF at 0° for 10 minutes. Themixture was diluted with water, extracted with ether and the extractwashed with water and dried over sodium sulfate. Evaporation of thesolvent and silica chromatography of the residue with 30% ethyl acetatein hexane gave 0.13 g. of the title product as an oil, λ_(max) ^(film)3.0 (shoulder), 3.45, 5.8, 10.35, 13.2, 14.3 μ. NMR: δ 7.18 (s, 5,aromatic), 6.25 (s, 2, OH), 5.42 (M, 4, olefinic), 4.02 (M, 1, 15-H)ppm. Mass spectrum: M⁺ at m/e 412.2587 (theory 412.2613).

EXAMPLE 11 7- 2-(3-S-Tetrahydropyran-2-Yloxy!-1-Octenyl-5-Oxo-3-Vinylcyclopentyl!-5-HeptenoicAcid

A solution of 9.0 ml. of 3.35M vinyl magnesium chloride in 40 ml. oftetrahydrofuran was added dropwise to an ice-cooled mixture of 1.0 g. of7- 2-(3-S-tetrahydropyran-2-yloxy!-1-octenyl)-5-oxo-3-cyclopenten-1-yl!-5-heptenoicacid and 2.0 g. of cuprous chloride in 40 ml. of tetrahydrofuran withstirring under nitrogen. After stirring for 0.5 hours at 0°, thereaction mixture was added to aqueous ammonium chloride solution andextracted with ether. After washing with water and drying over magnesiumsulfate, the extract was evaporated and the residue chromatographed onsilica. Elution with 20% ethyl acetate in hexane gave 0.3 g. of thetitle product as an oil, λ_(max) ^(film) 3.45, 5.75, 5.85, 6.1, 9.8,10.25, 11.0 μ.

EXAMPLE 12 7-2-(3-S-Hydroxy-1-Octenyl)-5-Oxo-3-Vinylcyclopentyl!-5-Heptenoic Acid

An ice-cooled solution of 0.30 g. of 7- 2-(3-S-tetrahydropyran-2-yloxy!-octenyl)-5-oxo-3-vinylcyclopentyl!-5-heptenoicacid in 20 ml. of THF was treated with 5.0 ml. of hydrochloric acid andthe mixture stirred at 0° for 5 minutes. The reaction mixture wasdiluted with water, extracted with ether and the extract washed withwater and dried over magnesium sulfate. Evaporation and silicachromatography of the residue with 30% ethyl acetate in hexane gave 0.10g. of the title product as an oil, λ_(max) ^(film) 3.0, 3.45, 5.8, 6.1,10.35, 11.0 μ. NMR: δ 4.5-5.8 (M, 7, olefinic H), 4.08 (M, 1, 15-H) ppm.Mass spectrum: M⁺ --H₂ O at m/e 344.2342 (theory 344.2350).

EXAMPLE 13 7-2-(3-S-Hydroxy-1-Octenyl)-3-Nitromethyl-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 0.70 g. of PGA₂ and 2.26 ml. of nitromethane in 25 ml. ofdry methanol was treated with 0.303 g. of sodium methylate and stirredat 25° under nitrogen for 2 hours. The reaction mixture was added towater, acidified with acetic acid and extracted with ether. Afterwashing with water and drying over sodium sulfate, the extract wasevaporated and the residue chromatographed on silica. Elution with 50%ethyl acetate-hexane gave 0.61 g. of the title product as an oil,λ_(max) ^(film) 3.0 (shoulder), 3.4, 5.75, 5.85, 6.45, 10.3 μ. NMR: δ6.42 (s, 2, OH), 5.60 (M, 2, 13 and 14-H), 5.40 (M, 2, 5 and 6-H), 4.47(M, 2, CH₂ NO₂), 4.15 (M, 1, 15-H) ppm. Mass spectrum: (M⁺ --H₂ O at m/e377.2225 (theory 377.2201).

EXAMPLE 14 7-2-(3-S-Hydroxy-1-Octenyl)-3-Methyl-5-Oxocyclopentyl!-5-Heptenoic Acid

A solution of 0.515 g. of PGA₂ in 20 ml. of THF was added dropwise over20 minutes to an ice-cooled stirring mixture of 7.5 ml. of 3MMeMgBr-ether and 1.58 g. of CuCl in 25 ml. of THF under nitrogen. Themixture was stirred at 0° for 15 minutes and at 25° for 15 minutes. Thereaction mixture was diluted with aqueous ammonium chloride solution,acidified with acetic acid and extracted with ether. After washing withwater and drying over sodium sulfate, the extract was evaporated and theresidue chromatographed on silica. Elution with 40% ethyl acetate inhexane gave 0.311 g. of the title product as an oil (solidified onstanding, m.p. 63°-68°), λ_(max) ^(KBr) 3.0, 3.5, 5.8, 8.5, 10.25 μ.NMR: δ 6.57 (s, 2, OH), 5.45 (M, 4, olefinic), 4.15 (M, 1, 15-H) ppm.Mass spectrum: M⁺ at m/e 350.2556 (theory 350.2456).

EXAMPLE 15 7-2-(3-S-Hydroxy-1-Octenyl)-5-Oxo-3-Phenylcyclopentyl!-5-Heptenoic Acid

A solution of 5.2 ml. of 2.5M phenyl magnesium bromide in 15 ml. of THFwas added dropwise over 15 minutes to an ice-cooled stirring mixture of0.60 g. of PGA₂ and 0.92 g. of cuprous chloride and the mixture stirredat 0° under nitrogen for 1 hour. The mixture was added to aqueousammonium chloride solution and extracted with ether. After washing withwater and drying over sodium sulfate, the extract was evaporated and theresidue chromatographed on silica. Elution with 30% ethyl acetate inhexane afforded 0.13 g. of the title product as an oil, λ_(max) ^(film)3.0 (shoulder), 3.45, 5.8, 10.3, 13.3, 14.3 μ. NMR: δ 7.22 (s, 5,aromatic), 5.42 (M, 4, olefinic), 4.02 (M, 1, 15-H) ppm. Mass spectrum:M⁺ --H₂ O at 394.2496 (theory 394.2507).

EXAMPLE 16 7-3-Benzyl-2-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-Heptenoic Acid

An ice-cooled mixture of 1.14 g. of PGA₂ and 1.75 g. of cuprous chloridein 50 ml. THF was treated with 10.3 ml. of 2.4M benzyl magnesiumchloride in THF and the mixture stirred at 0° for 1 hour under nitrogen.The reaction mixture was added to aqueous ammonium chloride solution,acidified with acetic acid and extracted with ether. After washing withwater and drying over sodium sulfate, the extract was evaporated and theresidue chromatographed on silica. Elution with 30% ethyl acetate inhexane gave 0.35 g. of the title product as an oil, λ_(max) ^(film) 3.0(shoulder), 3.45, 5.8, 6.2, 10.3, 13.3, 14.2 μ. NMR: δ 7.26 (s, 5,aromatic), 5.98 (s, 2, OH), 5.62 (M, 2, 13 and 14-H), 5.42 (M, 2, 5 and6-H), 4.17 (M, 1, 15-H), 2.29 (d, J=6, benzylic protons) ppm. Massspectrum: M⁺ at m/e 426.2749 (theory 426.2768).

EXAMPLE 17 7-3-Cyano-2-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-Heptenoic Acid,Methyl Ester, Acetate

A solution of 15.0 g. of 7-2-(3-S-hydroxy-1-octenyl)-5-oxo-3-cyclopenten-1-yl!-5-heptenoic acid,methyl ester, acetate 3.4 g. of potassium cyanide and 1.9 g. of ammoniumchloride in 500 ml. of dimethyl formamide and 100 ml. of water wasstirred at 90°-100° C. under nitrogen for 1 hour. After cooling, themixture was diluted with water, extracted with ether and the extractwashed with water and dried over sodium sulfate. Evaporation of thesolvent gave 15.5 g. of the title product as an oil, μ_(max) ^(film)3.45, 5.75, 7.3, 8.05, 9.85, 10.3 μ.

EXAMPLE 18

7- 3-Cyano-2-(3-S-Tetrahydropyran-2-Yloxy!-1-Octenyl)-5-Oxocyclopentyl!-5-Heptenoic Acid,Methyl Ester

A solution of 0.51 g. of 7- 2-(3-S- tetrahydropyran-2-yloxy!-1-octenyl)-5-oxo-3-cyclopenten-1-yl!-5-heptenoic acid, methyl ester 0.115 g. ofpotassium cyanide and 0.081 g. of ammonium chloride in 25 ml. ofdimethyl formamide and 5 ml. of water was stirred under nitrogen at90°-100° C. for 1 hour. After cooling to 25°, the mixture was added towater and extracted with ether. After washing with water and drying oversodium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 50% ethyl acetate in hexane gave0.237 g. of the title product as an oil, λ_(max) ^(film) 3.4, 4.45, 5.7,8.6, 9.75, 10.2, 11.5 μ. NMR: δ 5.1-5.9 (M, 4, olefinic), 4.70 (M, 1,O--CH--O), 3.80 (s, 3, OCH₃) ppm. Mass spectrum: M⁺ at m/e 459 (theory459), M⁺ --OPy at m/e 358.2423 (theory 358.2381).

EXAMPLE 19 7-3-Cyano-2-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-Heptenoic Acid

An ice-cooled solution of 0.57 g. of 7- 3-cyano-2-(3-S-tetrahydropyran-2-yloxy!-1-octenyl)-5-oxocyclopentyl!-5-heptenoic acid,methyl ester in 40 ml. THF was treated with 10 ml. of hydrochloric acidand the mixture stirred at 0° for 10 minutes. The reaction mixture wasadded to water, extracted with ether and the extract washed with waterand dried over sodium sulfate. Evaporation of the solvent gave an oilwhich was dissolved in 50 ml. of 0.5N sodium hydroxide in aqueousmethanol and kept at 25° for 0.5 hours. The solution was diluted withwater, acidified with hydrochloric acid and extracted with ether. Afterwashing with water and drying over sodium sulfate, the extract wasevaporated and the residue chromatographed on silica. Elution with 50%ethyl acetate in hexane gave 0.172 g. of the title product as an oil,λ_(max) ^(film) 3.0 (shoulder), 3.45, 4.45, 5.75, 7.1, 8.1, 10.3 μ. NMR:δ 6.50 (s, 2, OH), 5.82 (M, 2, 13 and 14-H), 5.42 (M, 2, 5 and 6-H),4.28 (M, 1, 15-H) ppm. Mass spectrum: M⁺ at m/e 361 (theory 361).

EXAMPLE 20 7-2-(3-S-Hydroxy-1-Octenyl)-3-Mercapto-5-Oxo-Cyclopentyl!-5-Heptenoic Acid

A solution of 1.12 g. of PGA₂ in 8 ml. of dry tetrahydrofuran wastreated at 0° C. with 1.5 g. of sodium sulfide in 6 ml. of water andstirred at 0° C. under nitrogen for one hour. The reaction mixture wasadded to water, acidified with acetic acid and extracted with ether.After washing with water and drying with magnesium sulfate, the extractwas evaporated and the residue chromatographed on silica. Elution with25% ethyl acetate in hexane gave 0.42 g. of the title product as an oil,λ_(max) ^(film) 3.00 (shoulder), 3.40, 4.00 (shoulder), 5.70, 5.85,7.10, 8.10, 10.3 μ. NMR: δ 4.30 (M, 1, 15-H), 5.50 (M, 2, 5 and 6-H),5.75 (M, 2, 13 and 14-H), 7.15 (s, 2, --OH) ppm. Mass spectrum: M⁺ atm/e 368.1960 (theory 368.2020).

EXAMPLE 21 7-3-Ethylthiol-2-(3-S-Hydroxy-1-Octenyl)-5-Oxo-Cyclopentyl!-5-HeptenoicAcid

A solution of 0.5 g. of PGA₂ in 2 ml. of ethanethiol was treated with0.1 ml. of piperidine and stirred at 25° C. for 20 hours. All thesolvent was removed in vacuum to give 0.61 g. of the title product as anoil, λ_(max) ^(film) 3.00 (shoulder), 3.50, 5.75, 5.85, 7.20, 8.10,10.40 μ. NMR: δ 4.20 (M, 1, 15-H), 5.42 (M, 2, 5 and 6-H), 5.70 (M, 2,13 and 14-H), 6.76 (s, 2, --OH) ppm. Mass spectrum: M⁺ at m/e 396(theory 396), M⁺ --H₂ O at m/e 378.2241 (theory 378.2228).

EXAMPLE 22 7-2-(3-S-Hydroxy-1-Octenyl)-5-Oxo-3-(Phenylthio)-Cyclopentyl!-5-HeptenoicAcid

A solution of 0.5 g. of PGA₂ and 0.2 g. of thiophenol in 6 ml. of drybenzene was treated with 0.1 ml. of piperidine and stirred at 25° C.under nitrogen for 20 hours. The reaction mixture was evaporated and theresidue was dissolved with ether. After washing with water and dryingover magnesium sulfate, the ether solution was evaporated and theresidue chromatographed on silica. Elution with 30% ethyl acetate inhexane gave 0.62 g. of the title product as an oil, λ_(max) ^(film) 3.00(shoulder), 3.50, 5.75, 5.85, 6.30, 10.40, 13.40, 14.50 μ. NMR: δ 4.12(M, 1, 15-H), 5.39 (M, 2, 5 and 6-H), 5.65 (M, 2, 13 and 14-H), 6.00 (S,2, --OH), 7.35 (M, 5, aromatic-H) ppm. Mass spectrum M⁺ at m/e 444.2334(theory 444.2381).

EXAMPLE 233-(6-Carboxy-2-Hexenyl)-α-Cyano-2-(3-S-Hydroxy-1-Octenyl)-4-Oxo-CyclopentaneAcetic Acid Ethyl Ester

A solution of 0.58 g. of PGA₂ and 0.185 ml. of ethyl cyano acetate in 25ml. of dimethylformamide was treated with 0.167 g. of 50% sodiumhydride-oil dispersion and the mixture stirred under nitrogen at 25° for0.5 hours. The mixture was diluted with water, acidified with aceticacid and extracted with ether. After washing with water and drying oversodium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 30% ethyl acetate in hexane gave0.435 g. of the title product as an oil, λ_(max) ^(film) 3.0 (shoulder),3.5, 4.3 and 4.45 (weak shoulder), 5.8, 8.0, 9.7, 10.3 μ. NMR: δ 6.38(S, 2, OH), 5.70 (M, 2, 13 and 14-H), 5.55 (m, 2, 5 and 6-H), 4.38 and3.58 (q, J=7.5, OCH₂), 1.25 (t, J=7.5, ester CH₃ ) ppm. Mass spectrum:M⁺ at m/e 447 (theory 447), M⁺ -H₂ O at m/e 429. 2529 (theory 429.2514).

EXAMPLE 243-(6-Carboxy-2-Hexenyl)-α-Cyano-2-(3-S-Hydroxy-1-Octenyl)-4-OxocylopentaneAcetic Acid

A solution of 1.424 g. of3-(6-carboxy-2-hexenyl)-α-cyano-2-(3-S-hydroxy-1-octenyl)-4-oxocyclopentaneacetic acid ethyl ester in 100 ml. of 0.5N sodium hydroxide in aqueousmethanol was stirred at 25° for 1 hour. The solution was diluted withwater, acidified with hydrochloric acid to pH 1 and extracted withether. After washing with water and drying over sodium sulfate, theextract was evaporated to obtain 1.19 g. of the title product as an oil,λ_(max) ^(film) 3.4, 4.3 and 4.45 (weak shoulder), 5.8, 7.1, 8.3, 10.3μ. NMR: δ 7.45 (S, 3, OH), 5.70 (M, 2, 13 and 14-H), 5.48 (M, 2, 5 and6-H), 4.25 (M, 1, 15-H), 3.95 (d, J=6, NC--CH--CO) ppm. Mass spectrum:M⁺ --CO₂ at m/e 375 (theory 375), M⁺ --CO₂ --H₂ O at m/e 356.2217(theory 356.2225).

EXAMPLE 253-(6-Carboxy-2-Hexenyl)-2-(3-S-Hydroxy-1-Octenyl)-4-Oxocyclopentyl!MalonicAcid 1,3-Diethyl Ester

A solution of 1.126 g. of PGA₂ and 0.51 ml. of diethyl malonate in 50ml. of dimethyl acetamide was treated with 0.334 g. of 50% sodiumhydride-oil dispersion and the mixture stirred at 25° for 0.5 hoursunder nitrogen. After diluting with water and acidifying with aceticacid, the mixture was extracted with ether and the extract washed withwater and dried over sodium sulfate. Evaporation of the solvent andsilica chromatography of the residue with 40% ethyl acetate in hexanegave 0.36 g. of the title product as an oil, λ_(max) ^(film) 3.0(shoulder), 3.5, 5.85, 8.7, 9.7, 10.4 μ. NMR: δ 5.3-5.7 (M, 4,olefinic), 4.22 (q, J=7.5, OCH₂), 3.55 (M, 1, CO--CH--CO), 1.25 (t,J=7.5, ester CH₃) ppm. Mass spectrum: M⁺ at m/e 494 (theory 494), M⁺ -H₂O at m/e 476.2773 (theory 476.2773).

EXAMPLE 263-(6-Carboxy-2-Hexenyl)-2-(3-S-Hydroxy-1-Octenyl)-4-Oxocyclopentyl!Malonic Acid

A solution of 0.28 g. of3-(6-carboxy-2-hexenyl)-2-(3-S-hydroxy-1-octenyl)-4-oxocyclopentyl!malonicacid 1,3-diethyl ester in 50 ml. of 0.5N sodium hydroxide in aqueousmethanol was stirred at 25° for 16 hours. The solution was diluted withwater, acidified with acetic acid to pH 4 and washed with ether. Thesolution was then acidified with hydrochloric acid to pH 1 and extractedwith ether. After washing with water and drying over sodium sulfate, theextract was evaporated to obtain 0.164 g. of the title compound as anoil (solidified on standing), λ_(max) ^(film) 3.5, 5.9, 7.15, 10.35 μ.NMR: δ 5.3-5.6 (M, 4, olefinic), 3.95 (M, 1, 15-H), 3.52 (M, 1,CO--CH--CO) ppm. Mass spectrum: M⁺ --CO₂ at m/e 394 (theory 394), M⁺--CO₂ --H₂ O at m/e 376.2231 (theory 276.2248).

EXAMPLE 27 7-3-Dicyanomethyl-2-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 1.0 g. of PGA₂ and 0.24 g. of malononitrile in 50 ml. ofdimethylformamide was treated with 0.28 g. of 50% sodium hydride-oildispersion and the mixture stirred under nitrogen at 25° for 0.5 hours.The mixture was diluted with water, acidified with acetic acid andextracted with ether. After washing with water and drying over sodiumsulfate, the extract was evaporated and the residue chromatographed onsilica. Elution with 35% ethyl acetate in hexane gave 0.8 g. of thetitle product as an oil, λ_(max) ^(film) 3.0 (shoulder), 3.5, 4.47, 5.8,7.12, 8.65, 10.3 μ. NMR: δ 5.78 (M, 2, 13 and 14-H), 5.48 (M, 2, 5 and6-H), 4.25 (M, 2, 15-H and CN--CH--CN) ppm. Mass spectrum: M⁺ at m/e 400(theory 400), M⁺ --H₂ O at m/e 382.2279 (theory 382.2255).

EXAMPLE 28 7-3-Cyanocarbamoylmethyl-2-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 1.2 g. of PGA₂ and 0.3 g. of 2-cyanoacetamide in 50 ml. ofdimethylformamide was treated with 0.34 g. of 50% sodium hydride-oildispersion and the mixture stirred under nitrogen at 25° for 0.5 hours.

The mixture was diluted with water, acidified with acetic acid andextracted with ether. After washing with water and drying over sodiumsulfate, the extract was evaporated and the residue chromatographed onsilica. Elution with ethyl acetate gave 0.58 g. of the title product asan oil, λ_(max) ^(film) 3.2 (shoulder), 3.5, 5.9, 7.45, 10.35 μ. NMR: δ7.58 (bs, 1, N-H), 7.12 (bs, 1, N-H), 5.25-5.65 (M, 4, olefinic), 3.95(M, 2, 15-H and CN--CH--CO) ppm. Mass spectrum: M⁺ --H₂ O at m/e 400(theory 400), M⁺ --H₂ O--CONH₂ at m/e 356.2234 (theory 356.2225).

EXAMPLE 29 7-3-Cyano-2-(3-R-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-Heptenoic Acid,Methyl Ester, Acetate

A solution of 1.06 g. of 15-epi-PGA₂, methyl ester, acetate and 0.25 g.of potassium cyanide in 25 ml. of dimethylformamide was treated with asolution of 0.18 g. of ammonium chloride in 7.0 ml. of water and themixture stirred at 100° for 1.5 hours under nitrogen. After cooling, thereaction mixture was added to water, acidified with hydrochloric acidand extracted with ether. After washing with water and drying oversodium sulfate, the extract was evaporated and the residuechromatographed on alumina (Activity 3). Elution with 20% ethyl acetatein hexane gave 0.77 g. of the title product as an oil, λ_(max) ^(film)3.4, 4.5, 5.7, 8.0, 9.75, 10.25 μ. NMR: δ 5.60-5.95 (M, 2, 5 and 6-H),5.05-5.60 (M, 3, 13, 14 and 15-H), 3.70 (S, 3, OCH₃), 2.10 (S, 3,acetate CH₃) ppm. Mass spectrum: M⁺ --CH₃ COOH at m/e 357 (theory 357).

EXAMPLE 30 7-2-(3-S-Hydroxy-1-Octenyl)-5-Hydroxy-3-Mercapto-Cyclopentyl!-5-HeptenoicAcid

A solution of 0.2 g. of 7-2-(3-S-hydroxy-1-octenyl)-3-mercapto-5-oxo-cyclopentyl!-5-heptenoic acidin 20 ml. of methanol was treated at 0° C with 0.6 g. of sodiumborohydride in 10 ml. of methanol and stirred at 0° C for one hour. Thereaction mixture was added to water, acidified with acetic acid andextracted with ether. After washing with water and drying with magnesiumsulfate, the extract was evaporated and the residue chromatographed onsilica. Elution with 30% ethyl acetate in hexane gave 0.09 g. of thetitle product as an oil, λ_(max) ^(film) 3.00 (shoulder), 3.40 3.90(shoulder), 5.85, 7.10, 8.20, 10.30 μ. NMR: δ 4.22 (M, 2, 9 and 15-H),5.02 (S, 2, -OH), 5.53 (M, 4, olefinic -H) ppm. Mass spectrum: M⁺ at m/e370 (theory 370), M⁺ --H₂ O at m/e 352.2139 (theory 352.2071).

EXAMPLE 31 3-Carbamoyl-2-(3-S-Hydroxyoctanyl)-5-Oxocyclopentyl HeptanoicAcid

A solution of 0.565 g. of 7-3-carbamoyl-2-(3-S-hydroxy-1-octenyl)-5-oxocyclopentyl!-5-heptenoic acidin 30 ml. of ethyl acetate was added to a prehydrogenated mixture of0.06 g. of 10% palladium on carbon in 30 ml. of ethyl acetate and themixture hydrogenated at 25° and atmospheric pressure until 2 equivalentsof hydrogen were absorbed. After filtering the catalyst, the solutionwas evaporated and the residue chromatographed on silica. Elution withethyl acetate gave 0.075 g. of the title product as an oil, λ_(max)^(film) 3.0, 3.5, 6.0, 7.0, 9.6 μ. Mass spectrum: M⁺ at m/e 383 (theory383), M⁺ --H₂ O at m/e 365.2589 (theory 365.2566).

EXAMPLE 32 3-Methyl-2-(3-S-Hydroxyoctyl)-5-Oxocyclopentyl Heptanoic Acid

A solution of 0.222 g. of 7-3-methyl-2-(3-S-hydroxy-1-octenyl)-5-oxocyclopentyl!-5-heptenoic acid in20 ml. of ethyl acetate was added to a prehydrogenated mixture of 0.045g. of 10% palladium on carbon in 20 ml. of ethyl acetate and the mixturehydrogenated at 25° and atmospheric pressure until 2 equivalents ofhydrogen were absorbed. After filtering the catalyst, the solution wasevaporated and the residue chromatographed on silica. Elution with 25%ethyl acetate in hexane gave 0.085 g. of the title compound as an oil(solidified on standing), λ_(max) ^(film) 3.0, 3.5, 5.8, 6.85, 8.5 μ.NMR: δ 6.12 (M, OH), 3.68 (M, 15-H), 1.12 (d, J=5.3, 11-CH₃) ppm. Massspectrum: M⁺ at m/e 354.2807 (theory 354.2768).

EXAMPLE 33 3-Carboxy-2-(3-S-Hydroxyoctyl)-5-Oxocyclopentyl HeptanoicAcid

A solution of 0.26 g. of 7-3-carboxy-2-(3-S-hydroxy-1-octenyl)-5-oxocyclopentyl!-5-heptenoic acidin 20 ml. of ethyl acetate was added to a prehydrogenated mixture of0.05 g. of 10% palladium on carbon in 20 ml. of ethyl acetate andhydrogenated at 25° and atmospheric pressure until 2 equivalents ofhydrogen were absorbed. After filtering the catalyst, the solution wasevaporated and the residue chromatographed on silica. Elution with 40%ethyl acetate in hexane gave 0.09 g. of the title compound as an oil,λ_(max) ^(film) 3.0 (shoulder), 3.45, 5.8, 7.1 μ. NMR: δ 7.88 and 7.68(M, OH), 3.68 (M, 15-H) ppm. Mass spectrum: M⁺ at m/e 284 (theory 284),M⁺ --H₂ O at m/e 366.2368 (theory 366.2405).

EXAMPLE 34 3-Benzyl-2-(3-S-Hydroxyoctyl)-5-Oxocyclopentyl Heptanoic Acid

A solution of 0.175 g. of 7-3-benzyl-2-(3-S-hydroxy-1-octenyl)-5-oxocyclopentyl!-5-heptenoic acid in15 ml. of ethyl acetate was added to a prehydrogenated mixture of 0.035g. of 10% palladium on carbon in 15 ml. of ethyl acetate and the mixturehydrogenated at 25° and atmospheric pressure until 2 equivalents ofhydrogen were absorbed. After filtering the catalyst, the solution wasevaporated and the residue chromatographed on silica. Elution with 30%ethyl acetate gave 0.082 g. of the title compound as an oil, λ_(max)^(film) 3.0 (shoulder), 3.5, 5.8, 6.23, 6.67, 6.88, 13.4, 14.34 μ. NMR:δ 7.30 (S, aromatic --H), 6.42 (S, OH), 3.65 (M, 15-H) ppm. Massspectrum: M⁺ at m/e 430.3098 (theory 430.3082).

EXAMPLE 35 7- 8-Cyano-7-(3-S-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4,4!Non-6-Yl!-5-Heptenoic Acid, Methyl Ester, Acetate

A solution of 15.3 g. of 7-3-cyano-2-(3-S-hydroxy-1-octenyl)-5-oxocyclopentyl!-5-heptenoic acid,methyl ester, acetate and 0.94 g. of p-toluenesulfonic acid in 920 ml.of benzene and 92 ml. of ethylene glycol was refluxed with a waterseparator for 24 hours. After cooling, the reaction mixture was dilutedwith ether, washed with water and dried over sodium sulfate. Evaporationof the solvent and silica chromatography of the residue with 20% ethylacetate in hexane gave 12.0 g. of the title product as an oil, λ_(max)^(film) 3.4, 4.45, 5.73, 8.1, 8.63, 9.7, 10.3 μ.

EXAMPLE 36 7- 8-Cyano-7-(3-S-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 12.0 g. of 7-8-cyano-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid, methyl ester, acetate in 330 ml. ofmethanol and 330 ml. of 1N sodium hydroxide was stirred at 25° for 1hour. The reaction mixture was diluted with water, acidified with aceticacid and extracted with ether. After washing with water and drying oversodium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 33% ethyl acetate in hexane gave9.4 g. of the title product as an oil, λ_(max) ^(film) 3.0 (shoulder),3.45, 4.45, 5.8, 8.65, 9.65, 10.3 μ. NMR: δ 7.1 (S, 2, OH), 5.70 (M, 2,13 and 14-H), 5.40 (M, 2, 5 and 6-H), 4.15 (M, 1, 15-H), 3.92 (S, 4,ketal H) ppm. Mass spectrum: M⁺ at m/e 405.2582 (theory 405.2514).

EXAMPLE 37 7- 8-Carboxy-7-(3-S-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-YL!-5-Heptenoic Acid and 7-8-Carbamoyl-7-(3S-Hydroxy-1-Octenyl-1,4-Dioxaspiro4.4!Non-6-YL!-5-Heptenoic Acid

A solution of 0.28 g. of 7-8-cyano-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 60 ml. of 0.5N sodium hydroxide inaqueous methanol was refluxed under nitrogen for 5 hours. The mixturewas cooled, diluted with water, acidified with acetic acid and extractedwith ether. After washing with water and drying over sodium sulfate, theextract was evaporated and residue chromatographed on silica. Elutionwith 50% ethyl acetate in hexane gave 0.115 g. of first title product asan oil, λ_(max) ^(film) 3.0 (shoulder), 3.45, 5.85, 8.7, 9.65, 10.3 μ.NMR: δ 5.68 (M, 4, olefinic), 4.12 (M, 15-H), 3.98 (S, 4, ketal) ppm.Mass spectrum: M⁺ at m/e 424.2462 (theory 424.2460).

Further elution with 1:2:97 acetic acid:methanol:ethyl acetate afforded0.10 g. of the second title product as an oil (solidified on standing),λ_(max) ^(film) 3.0 (shoulder), 3.45, 5.8, 8.7, 9.6, 10.3 μ. NMR: δ6.4-7.3 (M, 4, OH and NH), 5.60 (M, 4, olefinic), 4.05 (M, 5, 15-H andketal H) ppm. Mass spectrum: M⁺ at m/e 423.2674 (theory 423.2620).

EXAMPLE 38 7- 8-Formyl-7-(3-S-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 0.405 g. of 7-8-cyano-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid and 0.096 g. of 50% sodium hydride-oildispersion in 10 ml. of THF was added to a mixture of 5.0 ml. of 1Mlithium aluminum hydride and 0.73 ml. of ethyl acetate in 1.70 ml. ofTHF and stirred under nitrogen at 25° for 1 hour. The reaction mixturewas treated with 5 ml. of methanol, diluted with water, acidified withacetic acid and extracted with ether. After washing with water anddrying over sodium sulfate, the extract was evaporated to obtain 0.35 g.of the title product as an oil, λ_(max) ^(film) 3.0, 3.45, 5.8, 8.7,9.7, 10.3 μ. NMR: δ 9.50 (M, aldehyde H), 5.62 (M, 2, 13 and 14-H), 5.42(M, 2, 5 and 6-H), 4.10 (M, 1, 15-H), 3.92 (S, 4, ketal H) ppm.

EXAMPLE 39 7- 8-Hydroxymethyl-7-(3-S-Hydroxy-1-Octenyl-1,4-Dioxaspiro4.4!Non-6Yl!-5-Heptenoic Acid

A solution of 0.25 g. of 7-8-formyl-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 20 ml. of methanol was treated with asolution of 0.90 g. of sodium borohydride in 70 ml. of methanol and themixture stirred at 25° for 1 hour. After concentrating the mixture under40° under vacuum, the residue was diluted with water, washed with ether,acidified with acetic acid and extracted with ether. After washing withwater and drying over sodium sulfate, the ether extract was evaporatedto give 0.125 g. of the title product as an oil, λ_(max) ^(film) 3.25(shoulder), 3.5, 5.9, 7.2, 8.2 μ. Mass spectrum: M⁺ m/e 410.2724 (theory410.2666).

EXAMPLE 40 7- 8-Acetyl-7-(3-S-Hydroxy-1-Octenyl-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 0.623 g. of 7-8-cyano-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 35 ml. of THF was treated with 2.54ml. of 3M methyl magnesium bromide in ether and the mixture refluxedunder nitrogen for 1 hour. After cooling, the mixture was diluted withwater, acidified with acetic acid and extracted with ether. Afterevaporation of the ether, the residue was redissolved in 10 ml. of THFand 100 ml. of 0.5N sodium hydroxide. The solution was washed withether, acidified with acetic acid and extracted with ether. Afterwashing with water and drying over sodium sulfate, the extract wasevaporated and the residue chromatographed on silica. Elution with 40%ethyl acetate in hexane gave 0.10 g. of the title product as an oil,λ_(max) ^(film) 3.0, 3.4, 5.75, 8.55, 9.5 μ. NMR: δ 5.88 (M, 2, OH),5.68 (M, 2, 13 and 14-H), 5.42 (M, 2, 5 and 6-H), 4.10 (M, 1, 15-H),3.95 (S, 4, ketal), 2.15 (S, COCH₃) ppm. Mass spectrum: M⁺ at m/e422.2658 (theory 422.2666).

EXAMPLE 41 7- 8(1-Hydroxyethyl)-7-(3-S-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

An ice-cooled solution of 0.63 g. of 7-8-acetyl-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 40 ml. of methanol was treated with acold solution of 1.87 g. of sodium borohydride in 150 ml. of methanoland the mixture stirred at 25° for 1 hour. After concentrating themixture at 40° in vacuo, the residue was diluted with water, acidifiedwith acetic acid and extracted with ether. After washing with water anddrying over sodium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 60% ethyl acetate in hexane gave0.46 g. of the title product as an oil, λ_(max) ^(film) 3.2, 3.5, 5.9,9.7, 10.35 μ. Mass spectrum: M⁺ at m/e 424 (theory 424).

EXAMPLE 42 7- 8-Nitromethyl-7-(3-R-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid, Methyl Ester, Acetate

A solution of 1.0 g. of 7-2-(3-R-hydroxy-1-octenyl)-3-nitromethyl-5-oxocyclopentyl!-5-heptenoicacid, methyl ester, acetate and 0.125 g. of p-toluenesulfonic acid in125 ml. of benzene and 12.0 ml. of ethylene glycol was refluxed with awater separator for 20 hours. After cooling, the mixture was dilutedwith ether, washed with water and dried over sodium sulfate. Evaporationof the solvent and silica chromatography of the residue with 30% ethylacetate in hexane gave 0.685 g. of the title product as an oil, λ_(max)^(film) 3.45, 5.8, 6.5, 7.0, 7.35, 8.15, 9.9, 10.35 μ. NMR: δ 5.0-5.6(M, 5, olefinic and 15-H), 4.28 (m 2, CH₂ NO₂), 3.90 (S, 4, ketal), 3.68(S, 3, OCH₃), 2.02 (S, COCH₃) ppm. Mass spectrum: M⁺ at m/e 495 (theory495), M⁺ -CH₃ COOH at m/e 435.2636 (theory 435.2620).

EXAMPLE 43 7- 8-Nitromethyl-7-(3-R-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 4.5 g. of 7-8-nitromethyl-7-(3-R-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid, methyl ester, acetate in 150 ml. ofmethanol and 120 ml. of 1N sodium hydroxide was stirred under nitrogenat 25° for 1 hour. The solution was diluted with water, acidified withacetic acid and extracted with ether. After washing with water anddrying over sodium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 30% ethyl acetate in hexane gave3.68 g. of the title product as an oil (solidified on standing), λ_(max)^(KBr) 3.0, 3.45, 5.85, 6.45, 6.9, 7.95, 9.15, 10.25 μ. NMR: δ 6.55 (S,2, OH), 5.62 (M, 4, olefinic), 4.30 (M, 3, 15-H and CH₂ NO₂), 3.92 (S,4, ketal) ppm. Mass spectrum: M⁺ at m/e 439 (theory 439), M⁺ -NO₂ at m/e393.2651 (theory 393.2639).

EXAMPLE 44 7- 8α-Cyano-7-(3-R-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid, Methyl Ester, Acetate and 7-8β-Cyano-7-(3-R-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid, Methyl Ester, Acetate

A solution of 3.4 g. of 7-3-cyano-2-(3-cyano-2-(3-R-hydroxy-1-octenyl)-5-oxocyclopentyl!-5-heptenoicacid, methyl ester, acetate and 0.15 g. of p-toluenesulfonic acid in 150ml. of benzene and 15 ml. of ethylene glycol was refluxed with a waterseparator for 22 hours. After cooling, the reaction mixture was dilutedwith ether, washed with water and dried over sodium sulfate. Evaporationof the solvent and silica chromatography of the residue with 25% ethylacetate in hexane gave 1.19 g. of the first title product as an oil,λ_(max) ^(film) 3.45, 4.5, 5.75, 8.1, 9.8, 10.3 μ. NMR: δ 5.5-5.7 (M, 2,5 and 6-H), 5.0-5.5 (M, 3, 13, 14 and 15-H), 3.93 (S, 4, ketal), 3.68(S, 3, OCH₃), 2.03 (S, acetate CH₃) ppm. Mass spectrum: M⁺ at m/e 461(theory 461), M⁺ -HC₂ H₃ O₂ at m/e 401.2557 (theory 401.2565).

Further elution with 25% ethyl acetate in hexane afforded 0.93 g. of thesecond title product as an oil, λ_(max) ^(film) 3.45, 4.5, 5.75, 8.1,9.8, 10.3 μ. NMR: 5.55-5.95 (M, 2, 5 and 6-H), 5.05-5.55 (M, 3, 13, 14and 15-H), 3.92 (S, 4, ketal), 3.68 (S, 3, OCH₃), 3.07 (q, J=7.5, 11-H),2.05 (S, acetate CH₃) ppm. Mass spectrum: M⁺ at m/e 461 (theory 461), M⁺HC₂ H₃ O₂ at m/e 401.2532 (theory 401.2565).

EXAMPLE 45 7- 8α-Cyano-7-(3-R-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

(A) A solution of 1.10 g. of 7-8α-cyano-7-(3-R-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid, methyl ester, acetate in 25 ml. ofmethanol was treated with 25 ml. of 1N sodium hydroxide and the mixturestirred at 25° under nitrogen for 1 hour. The mixture was diluted withwater, acidified with acetic acid and extracted with ether. Afterwashing with water and drying over sodium sulfate, the extract wasevaporated and the residue chromatographed on silica. Elution with 30%ethyl acetate in hexane followed by crystallization from ethyl acetateand pentane afforded 0.37 g. of the title product, m.p. 88.5°-89.5°,mixed m.p. with the 8β isomer 75°-80°, λ_(max) ^(KBr) 3.15, 4.0, 5.85,7.2, 8.1, 8.7, 9.6, 10.4, 11.0, 14.2 μ. NMR: 7.35 (S, 2, OH), 5.1-5.9(M, 4, olefinic H), 4.12 (M, 1, 15-H), 3.95 (S, 4, ketal H) ppm. Massspectrum: M⁺ at m/e 405 (theory 405 (theory 405), M⁺ -H₂ O at m/e387.2379 (theory 387.2409).

(B) A solution of 0.20 g. of 7-8β-cyano-7-(3-R-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 20 ml. of tertiary butyl alcohol wastreated with 0.28 g. of potassium tertiary butoxide and the mixturestirred at 25° under nitrogen for 16 hours. Following dilution withwater and acidification with acetic acid, the mixture was extracted withether and the extract washed with water and dried over sodium sulfate.Evaporation of the solvent and silica chromatography with 50% ethylacetate in hexane gave 0.16 g. of the title product as white crystals. Arecrystallized sample (ethyl acetate-pentane) exhibited m.p. 84-86,mixed m.p. with authentic 8α-isomer 87°-89° and mixed m.p. with8β-isomer 73°-76°.

EXAMPLE 46 7- 8β-Cyano-7-(3-R-HYdroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 0.83 g. of 7-8β-cyano-7-(3-R-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid, methyl ester, acetate in 25 ml. ofmethanol was treated with 25 ml. of lN sodium hydroxide and the mixturestirred at 25° under nitrogen for 1 hour. The solution was diluted withwater, acidified with acetic acid and extracted with ether. Afterwashing with water and drying over sodium sulfate, the extract wasevaporated and the residue chromatographed on silica. Elution with 30%ethyl acetate - hexane followed by crystallization from ethyl acetateand pentane afforded 0.23 g. of the title product, m.p. 88°-89°, mixedm.p. with the 8α isomer 75°-80°, λ_(max) ^(KBr) 3.1, 3.45, 5.95, 7.55,7.65, 7.85, 8.7, 9.6, 10.35, 11.0, 13.25 μ. NMR: 7.23 (S, 2, OH), 5.70(M,2, 5 and 6-H), 5.45 (M, 2, 13 and 14-H), 4.20 (M, 1, 15-H), 3.95 (S,4, ketal H), 3.08 (q, J=7.3, 11-H) ppm. Mass spectrum: M⁺ at m/e 405(theory 405), M⁺ -H₂ O 387.2417 (theory 387-2409)

EXAMPLE 47 7-3-Carboxy-2-(3-S-Hydroxy-1-Octenyl-5-Oxocyclopentyl!-5-Heptenoic Acid

A solution of 0.70 g. of 7-8-carboxy-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 50 ml. of THF and 5.0 ml. ofhydrochloric acid was stirred at 25° for 0.5 hours. The mixture wasdiluted with water, extracted with ether and the extract washed withwater and dried over sodium sulfate. Evaporation of the solvent andsilica chromatography of the residue with 50% ethyl acetate in hexanegave 0.45 g. of the title product as an oil, λ_(max) ^(film) 3.5, 5.85,7.15, 8.2, 10.4 μ. NMR: δ5.68 (M, 2, 13 and 14-H), 5.45 (M, 2, 5 and6-H), 4.20 (M, 1, 15-H) ppm. Mass spectrum: M⁺ at m/e 380 (theory 380),M⁺ -H₂ O at m/e 362.2123 (theory 362.2093).

EXAMPLE 48 7-3-Carbamoyl-2-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-Heptenoic Acid

A solution of 0.51 g. of 7-8-carbamoyl-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 50 ml. of THF and 5.0 ml. ofhydrochloric acid was stirred at 25° hours. The mixture was diluted withwater, extracted with ether and the extract washed with water and driedover sodium sulfate. Evaporation of the solvent and silicachromatography of the residue with 1:2:97 acetic acid: methanol:ethylacetate gave 0.38 g. of the title product as an oil, λ_(max) ^(film)3.0, 3.4, 5.7, 5.9, 6.1 (shoulder), 8.0, 10.3 μ. NMR: δ 6.4-6.9 (M, 4,OH and NH), 5.65 (M, 2, 13 and 14-H), 5.42 (M, 2, 5 and 6-H), 4.15 (M,1, 15-H) ppm. Mass spectrum: M⁺ at m/e 379 (theory 379), M⁺ -2H₂ O atm/e 343.2155 (theory 343.2146).

EXAMPLE 49 7-3-Hydroxymethyl-2-(3-S-Hydroxy-1-Octenyl-5-Oxocyclopentyl!-5-HeptenoicAcid

An ice-cooled solution of 0.255 g. of 7-8-hydroxymethyl-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 25 ml. of THF was treated with 2.5 ml.of hydrochloric acid and the mixture stirred at 0° for 0.5 hours. Thereaction mixture was diluted with ether, washed with water, dried oversodium sulfate and evaporated. Silica chromatography of the residue with70% ethyl acetate in hexane gave 0.056 g. of the title product as anoil, λ_(max) ^(film) 3.0, 3.45, 5.8, 7.1, 8.1, 10.3 μ. NMR: 67 5.1-5.8(M, 7, 4-olefinic H, 3-OH), 4.12 (M, 1, 15-H), 3.72 (M, 2, O-CH₂) ppm.Mass spectrum: M⁺ at m/e 366 (theory 366), M⁺ -C₅ H₁₁ at m/e 295.1551(theory 295.1544).

EXAMPLE 50 7- 3-Acetyl-2-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-Heptenoic Acid

A solution of 0.16 g. of 7-8-acetyl-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 15 ml. of THF and 1.5 ml. ofhydrochloric acid was stirred at 25° for 0.5 hours. The mixture wasdiluted with water, extracted with ether and the extract washed withwater and dried over sodium sulfate. Evaporation and silicachromatography of the residue with 40% ethyl acetate in hexane gave 0.13g. of the title product as an oil, λ_(max) ^(film) 3.0, 3.45, 5.8, 7.1,8.6, 10.3 μ. NMR: δ 6.12 (S, 2, OH), 5.68 (M, 2, 13 and 14-H), 5.42 (M,2, 5 and 6-H), 4.20 (M, 1, 15-H), 2.20 (S, COCH₃) ppm. Mass spectrum: M⁺at m/e 378.2438 (theory 378.2405).

EXAMPLE 51 7-3-(1-Hydroxyethyl)-7-(3-S-Hydroxy-1-Octenyl)-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 0.46 g. of 7-8-(1-hydroxyethyl)-7-(3-S-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 30 ml. of THF and 3.0 ml. ofhydrochloric acid was stirred at 25° for 0.5 hours. The mixture wasdiluted with water, extracted with ether and the extract washed withwater and dried over sodium sulfate. Evaporation of the solvent andsilica chromatography of the residue with 50% ethyl acetate in hexanegave 0.14 g. of the title product as an oil, λ_(max) ^(film) 3.0, 3.5,5.85, 7.15, 8.2, 10.4 μ. NMR: δ 5.50 (M, 4, olefinic), 4.02 (M, 2,O-CH), 1.20 (d, J=6, Me-CH) ppm. Mass spectrum: M⁺ -H₂ O at m/e 362(theory 362), M⁺ -2H₂ O at m/e 344.2367 (theory 344.2350).

EXAMPLE 52 7- 8-Nitromethyl- 7-(3-Oxo-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 0.2 g. of 7-8-nitromethyl-7-(3-R-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 5 ml. of acetone was treated at -10°with 0.1 ml. of Jones reagent and stirred at 0° C. for 15 minutes.Following the addition of 1 ml. of methanol, the reaction mixture wasbasified with aqueous sodium bicarbonate solution, acidified with aceticacid and extracted with ether. After washing with water and drying withmagnesium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 30% ethyl acetate in hexane gave0.17 g. of the title product as a semi-solid, λ_(max) ^(film) 3.50,5.87, 6.15 (shoulder), 6.45, 7.25 μ. NMR: δ 3.95 (S, 4, ketal), 4.30 (M,2, --CH₂ NO₂), 5.20-5.80 (M, 3, 5, 6 and 14-H), 6.20-2.90 (M, 1, 13-H),8.28 (S, 1, OH) ppm. UVλ_(max) ^(EtOH) 223 mμ (ε 8,740). Mass spectrum:M⁺ at m/e 437.2456 (theory 437.2480).

EXAMPLE 53 7- 8α-Cyano-7-(3-Oxo-1-Octenyl)-1,4-Dioxaspiro 4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 1.0 g. of 78α-cyano-7-(3-R-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 50 ml. of acetone was treated at 0°with 3.4 ml. of 1.2M Jones reagent and stirred at 0° C. under nitrogenfor 3/4 hours. The reaction mixture was treated with 3 ml. of ethanoland neutralized with aqueous sodium bicarbonate solution. Afteracidification by acetic acid, the mixture was extracted with ether andthe extract washed with brine and dried with magnesium sulfate. Theextract was evaporated and the residue chromatographed on silica.Elution with 35% ethyl acetate-hexane gave 0.95 g. of the title productas an oil, λ_(max) ^(film) 3.5, 4.5, 5.8 (shoulder), 5.85, 6.10, 8.60,9.70 μ. UV δ_(max) ^(EtOH) 225 mμ (δ13,000). NMR: λ 3.95 (S, 4, ketal),5.42 (M, 2, 5 and 6-H), 6.42 (M, 2, 13 and 14-H), 9.65 (M, 1, --OH) ppm.Mass spectrum: M⁺ at m/e 403.2334 (theory 403.2357).

EXAMPLE 54 7- 8β-Cyano-7-(3-Oxo-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 4.05 g. of 7-8β-cyano-7-(3-R-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 50 ml. of acetone was treated at 0° C.with 3.5 mls. of 1.2 M Jones reagent and stirred at 0° C. for 3/4 hour.The reaction mixture was treated with 3 ml. of ethanol and neutralizedwith aqueous sodium bicarbonate solution. After acidification withacetic acid, the mixture was extracted with ether and the extract washedwith brine and dried with magnesium sulfate. Evaporation of the driedether extract gave 4.00 g. of the title product as a solid, which wasrecrystallized from ether-pentane mixture to give white crystals, m.p.52°-54° C., λ_(max) ^(film) 3.45, 4.50, 5.70 (shoulder), 5.85, 6.10,8.70, 9.70 μ. UV λ_(max) ^(EtOH) 225 mμ (μ11,000). NMR: δ 3.21 (q,J=7.5, 11-H), 4.00 (S, 4, ketal), 5.46 (M, 2, 5 and 6-H), 6.22 (d, J=16,14-H), 6.98 (dd, J=9, 16, 13-H). Mass spectrum: M⁺ at m/e 403.2357(theory 403.2357).

EXAMPLE 55 7-8-Nitromethyl-7-(3-Methyl-3-Hydroxy-1-Octenyl)-1,4-Dioxaspiro 4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 1.72 g. of 7-8-nitromethyl-7-(3-oxo-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 80 ml. of tetrahydrofuran was treatedat -10° C. with 9.7 ml. of 3M methyl magnesium bromide intetrahydrofuran and was stirred at 0° C. for 1 hour. The reactionmixture was added to aqueous ammonium chloride solution, acidified withacetic acid and extracted with ether. After washing with water anddrying over magnesium sulfate, the extract was evaporated and theresidue chromatographed on silica. Elution with 30% ethyl acetate inhexane gave 0.26 g. of the title product as an oil, λ_(max) ^(film) 3.00(shoulder), 3.45, 5.80 (shoulder), 5.85, 6.45, 7.25, 10.30 μ. NMR: δ1.32 (S, 15-methyl), 4.01 (S, 4, ketal), 4.40 (M, 2, CH₂ NO₂), 5.22 (M,2, 5 and 6-H), 5.63 (M, 2, 13 and 14-H) ppm. Mass spectrum: M⁺ at m/e453), (theory 453), M⁺ -H₂ O at m/e 435.2571 (theory 435.2620).

EXAMPLE 56

7- 8-Nitromethyl-7-(3-Hydroxy-3-Phenyl-(1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 1.88 g. of 7-8-nitromethyl-7-(3-oxo-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 80 ml. of tetrahydrofuran was treatedat -10° C. with 6.6 ml. of 3M phenyl magnesium bromide intetrahydrofuran and was stirred at 0° C. for one hour. The reactionmixture was added to aqueous ammonium chloride solution, acidified withacetic acid and extracted with ether. After washing with water anddrying with magnesium sulfate, the extract was evaporated and theresidue chromatographed on silica. Elution with 30% ethyl acetate inhexane gave 0.90 g. of the title product as an oil, λ_(max) ^(film) 3.00(shoulder), 3.50, 5.88, 6.28, 6.47, 6.95, 7.25, 13.30, 14.35 μ. NMR: δ3.93 (S, 4, ketal), 4.35 (M, 2, -CH₂ NO₂), 5.15-6.05 (M, 4, olefinic-H), 5.88 (S, 2,-OH), 7.45 (M, 5, aromatic-HO ppm. Mass spectrum: M⁺ atm/e 515 (theory 515), M⁺ -H₂ O at m/e 497.2776 (theory 497.2776.

EXAMPLE 57 7- 8α-Cyano-7-(3-Methyl-3-Hydroxy-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl!-5-Heptenoic Acid

A solution of 0.98 g. of 7- 8α-cyano-7-(3-oxo-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 35 ml. of dry tetrahydrofuran wastreated under nitrogen at -10° C. with 5 ml. of 3M methyl magnesiumbromide in tetrahydrofuran and stirred at -10° C for 11/2 hours. Thereaction mixture was added to 20 ml. of saturated aqueous ammoniumchloride solution, acidified with acetic acid and extracted with ether.After washing with brine and drying with magnesium sulfate, the etherextract was evaporated to give 1.02 g. of the title product as an oil,λ_(max) ^(film) 3.0 (shoulder), 3.5, 4.4, 5.8, 8.7, 9.4 μ. NMR: δ 1.32(S, 15-CH₃), 4.01 (S, 4, ketal), 5.50-5.80 (M, 4, olefinic H), 6.88 (S,2, -OH) ppm. Mass spectrum: M⁺ at m/e 419.2679 (theory 419.2671).

EXAMPLE 58 7- 8β-Cyano-7-(3-Hydroxy-3-Methyl-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6-Yl)-5-Heptenoic Acid

A solution of 0.87 g. of 7- 8β-cyano-7-(3-oxo-1-octenyl)1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 35 ml. of THF was treated undernitrogen at 0° C. with 5 ml. of 3M methyl magnesium bromide in THF andstirred at 0° C. for 1/2 hours. The reaction mixture was added to 20 ml.of saturated aqueous ammonium chloride solution, acidified with aceticacid and extracted with ether. After washing with brine and drying withmagnesium sulfate, the ether extract was evaporated and the residuechromatographed on silica. Elution with 20% ethyl acetatehexane gave0.54 g. of 7- 8α-cyano-7-(3-hydroxy-3-methyl-1-octenyl)-1,4-dioxaspiro4.4!-non-6-yl!-5-heptenoic acid. Continued elution with 20% ethylacetate-hexane gave 0.08 g. of the title product as an oil, λ_(max)^(film) 2.95 (shoulder), 3.40, 4.40, 5.80, 8.65, 9.60 μ. NMR: δ 1.30 (S,15-methyl), 3.10 (q J=7.5, 11-H), 3.92 (S, 4, ketal), 5.40 (M, 2, 5 and6-H), 5.70 (d, 2, J=4, 13 and 14-H), 6.10 (S, 2, -OH). Mass spectrum: M⁺at m/e 419 (theory 419), M⁺ -H₂ O at m/e 401.2557 (theory 401.2565).

EXAMPLE 59 7-2-(3-Hydroxy-3-Methyl-1-Octenyl)-3-Nitromethyl-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 0.20 g. of 7-8-nitromethyl-7-(3-methyl-3-hydroxy-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 4 ml. of tetrahydrofuran was treatedat 0° C. with 0.4 ml. of concentrated hydrochloric acid and stirred at0° C. for 1.5 hours. The reaction mixture was added to water andextracted with ether. After washing with water and drying over magnesiumsulfate, the extract was evaporated and the residue chromatographed onsilica. Elution with 15% ethyl acetate in hexane gave 0.11 g. of thetitle product as an oil, λ_(max) ^(film) 3.00 (shoulder), 3.50, 5.80,6.45, 7.25, 10.30 μ. NMR: δ 1.32 (S, 15-methyl), 4.49 (M, 2, --CH₂ NO₂),5.80 (M, 4, olefinic --H), 5.92 (S, 2, OH) ppm. Mass spectrum: M⁺ -H₂ Oat m/e 391.2402 (theory 391.2358).

EXAMPLE 60 7-2-(3-Hydroxy-3-Phenyl-1-Octenyl)-3-Nitromethyl-5-Oxo-Cyclopentyl!-5-HeptenoicAcid

A solution of 0.3 g. of 7-8-nitromethyl-7-(3-hydroxy-3-phenyl-1-octenyl)-1,4-dioxaspiro4.4!-non-6-yl!-5-heptenoic acid in 6 ml. of dry tetrahydrofuran wastreated at 0° C. with 0.6 ml. of concentrated hydrochloric acid andstirred at 0° C. for 1.5 hours. The reaction mixture was added to waterand extracted with ether. After washing with water and drying overmagnesium sulfate, the extract was evaporated and the residuechromatographed on silica. Elution with 33% ethyl acetate in hexane gave0.08 g. of the title product as an oil, λ_(max) ^(film) 3.00 (shoulder),3.40, 5.75, 6.40, 7.20, 10.20, 13.20, 14.18 μ. NMR: δ 4.45 (m, 2, --CH₂NO₂), 5.40 (m, 2, 5 and 6-H), 5.85 (m, 2, 13 and 14-H), 5.90 (s, 2, OH),7.40 (s, 5, aromatic -H) ppm. Mass spectrum: M⁺ at m/e 471 (theory 471),M⁺ -H₂ O at m/e 453 (theory 453).

EXAMPLE 61 7-3α-Cyano-2-(3-Hydroxy-3-Methyl-1-Octenyl)-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 0.30 g. of 7-8α-cyano-7-(3-hydroxy-3-methyl-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 12 ml. of THF was treated undernitrogen at 25° with 2.8 ml. of 3M perchloric acid and stirred for 6hours. The reaction mixture was added to water and extracted with ether.After washing with brine and drying with magnesium sulfate, the etherextract was evaporated and the residue chromatographed on silica.Elution with 30% ethyl acetate in hexane gave 0.18 g. of the titleproduct as an oil, λ_(max) ^(film) 3.0 (shoulder), 3.4, 4.45, 5.75,8.75, 10.3 μ. NMR: Γ 1.33 (S, 15-methyl), 5.54 (M, 2, 5 and 6-H), 5.82(M, 2, 13 and 14-H), 6.70 (M, 2, -OH) ppm. Mass spectrum: M⁺ at m/e 375(theory 375), M⁺ -H₂ O at m/e 357.2303 (theory 357.2314).

EXAMPLE 62 7-3β-Cyano-2-(3-Hydroxy-3-Methyl-1-Octenyl)-5-Oxocyclopentyl!-5-HeptenoicAcid

A solution of 0.8 g. of 7-8β-cyano7-(3-hydroxy-3-methyl-1-octenyl)-1,4-dioxaspiro4.4!non-6-yl!-5-heptenoic acid in 16 ml. of THF was treated undernitrogen at 25° with 4 ml. of 3M perchloric acid and stirred for tenhours. The reaction mixture was added to water and extracted with ether.After washing with brine and drying with magnesium sulfate, the etherextract was evaporated and the residue chromatographed on silica.Elution with 35% ethyl acetate in hexane gave 0.68 g. of the titleproduct as an oil, λ_(max) ^(film) 2.95 (shoulder), 3.40, 4.40, 5.75,7.00, 8.50, 10.15 μ. NMR: δ 1.35 (S, 15-methyl), 3.40 (M, 1, 11-H), 5.49(M, 2, 5 and 6-H), 5.88 (d, J=4, 13 and 14-H), 6.41 (S, 2, --OH)ppm.Mass spectrum: M⁺ at m/e 375.2347 (theory 375.2409).

EXAMPLE 63 3α-Cyano-2-(3-Hydroxy-3-Methyl Octyl-5-OxocyclopentylHeptanoic Acid

A solution of 0.29 g. of 7-3α-cyano-2-(3-hydroxy-3-methyl-1-octenyl)-5-oxocyclopentyl!-5-heptenoicacid in 15 ml. of ethyl acetate was added to a prehydrogenated mixtureof 0.18 g. of 10% Pd/C in 15 ml. of ethyl acetate and the mixturehydrogenated at 25° and atmospheric pressure until 2 equivalents ofhydrogen were absorbed. After filtering, the solution was evaporated andthe residue chromatographed on silica. Elution with 30% ethyl acetate inhexane afforded 0.18 g. of the title product as an oil, λ_(max) ^(film)3.0 (shoulder), 3.4, 4.4, 5.7, 6.75, 8.1, 8.55, 10.7 μ. NMR: δ 6.10 (S,2, OH), 1.22 (S, 15-CH₂) ppm. Mass spectrum: M⁺ -H₂ O at m/e 361.2579(theory 361.2617).

EXAMPLE 64 3β-Cyano-2-(3-Hydroxy-3-Methyl-Octyl)-5-OxocyclopentylHeptanoic Acid

A solution of 0.18 g. of 7-3β-cyano-2-(3-hydroxy-3-methyl-1-octenyl)-5-oxocyclopentyl!-5-heptanoicacid in 20 ml. of ethyl acetate was added to a prehydrogenated mixtureof 0.08 g. of 10% Pd/C in 10 ml of ethyl acetate and the mixturehydrogenated at 25° and atmospheric pressure until 2 equivalents ofhydrogen were absorbed. After filtering, the solution was evaporated andthe residue chromatographed on silica. Elution with 30% ethyl acetate inhexane afforded 0.15 g. of the title product as an oil, λ_(max) ^(film)3.0 (shoulder), 3.45, 4.45, 5.80, 6.80, 8.60, 10.9 μ. NMR: δ 1.25 (S,15-methyl), 3.41 (M, 1, 11-H), 6.10 (S, 2, --OH) ppm. Mass spectrum: M⁺-H₂ O at m/e 361.2601 (theory 361.2617).

EXAMPLE 65 7- 2β-(3S)-3-Hydroxy-Trans-1-Octenyl!-3α-Methyl-5-Oxo-1α-Cyclopentyl!-Cis-5-HeptenoicAcid and 7- 2β-(3S)-3-Hydroxy-Trans-1-Octenyl!-3β-Methyl-5-Oxo-1α-Cyclopentyl!-Cis-5-HeptenoicAcid

A solution of 3.0 g. of PGA₂ in 60 ml. of tetrahydrofuran (THF) wasadded dropwise to an ice-cooled mixture of 24 ml. of 3M methyl magnesiumbromide and 5.0 g. of cuprous chloride in 120 ml. of THF and stirred at0° C. for 1 hour. The mixture was added to aqueous ammonium chloridesolution and extracted with ether. After washing with water and dryingover magnesium sulfate, the extract was concentrated to give crystallinematerial. Filtration followed by recrystallization from ether-pentaneafforded 1.2 g. of the first title product, m.p. 68°-70° C., λ_(max)^(KBr) 3.0 (shoulder), 3.5, 5.8, 6.9, 7.6, 8.05, 8.55, 10.3 μ. NMR: δ6.93, (s, 2, OH), 5.54 (m, 13 and 14-H), 5.38 (m, 5 and 6-H), 4.16 (m,1, 15-H). Mass spectrum: M+ at m/e 350.2476 (theory 350.2455).

Evaporation of the filtrates and silica chromatography of the residuewith 30% ethylacetate in hexane followed by crystallization fromether-pentane gave 0.09 g. of the second title product, m.p. 72°-74° C.,λ_(max) ^(film) 3.0 (shoulder), 3.5, 5.8 (shoulder), 5.9, 7.0, 8.15,8.45, 10.4 μ. NMR: δ 7.05-6.22 (m, 2, OH), 5.48 (m, 4, olefinic), 4.15(m, 1, 15-H) ppm. Mass spectrum: M⁺ at m/e 350.2460 (theory 350.2455).

EXAMPLE 66 2β- (3S)-3-Hydroxyoctyl!-3α-Methyl-5-Oxo-1α-CyclopentaneHeptanoic Acid

A solution of 0.9 g. of 7-(2β-(3S)-3-hydroxy-transoctenyl!-3α-methyl-5-oxo-1α-cyclopentyl)-cis-5-heptenoicacid in 10 ml. of methanol was added to a prehydrogenated mixture of 0.2g. of 5% Pd/C in 155 ml. of methanol and the mixture hydrogenated at 25°and atmospheric pressure until two equivalents of hydrogen wereabsorbed. After filtering, the solution was evaporated and the residuechromatographed on silica. Elution with 25% ethylacetate in hexanefollowed by recrystallization from ethylacetate-hexane afforded 0.25 g.of the title product, m.p. 43.5-44.5° C., λ_(max) ^(KBr) 3.0, 3.5, 5.8,6.85, 8.5, 8.9 μ. NMR: ∥ 6.81 (s, 2, OH), 3.65 (m, 1, 15-H) ppm. Massspectrum: M⁺ at m/e 354.2771 (theory 354.2768).

EXAMPLE 67

7-(5α-Hydroxy-2β-(3S)-3-Hydroxy-Trans-1-Octenyl!-3α-Methyl-1α-Cyclopentyl)-Cis-5-HeptenoicAcid and

7-(5β-Hydroxy-2β-(3S)-3-Hydroxy-1-Octenyl!-3α-Methyl-1.alpha.-Cyclopentyl)-Cis-5-HeptenoicAcid

An ice-cooled solution of 7.8 g. of 7-(2β-(3S)-3-hydroxy-trans-1-octenyl!-3α-methyl-5-oxo-1α-cyclopentyl)-cis-5-heptenoicacid in 150 ml. of methanol was treated with 3.5 g. of sodiumborohydride and stirred at 0° C. for 2 hours. The mixture was dilutedwith water and acidified with acetic acid. Extraction of the resultingmixture with ether, followed by washing, drying and evaporation of theextract gave the crude product. Silica chromatography with 30% ethylacetate in hexane afforded 3.5 g. of the first title product as an oil,λ_(max) ^(film) 3.0, 3.5, 5.85, 6.9, 7.15, 8.1, 8.9, 9.8, 10.35 λ. NMR:δ 5.57 (s, 3,OH), 6.0-5.17 (m, 4, olefinic), 4.21 (m, 2, 9 and 15-H),1.01 (d, J=4.5, 11-methyl) ppm. Mass spectrum: M⁺ H at m/e 352.2670(theory 352.2613).

Further elution with 30% ethyl acetate in hexane afforded 3.0 g. of thesecond title product as an oil, λ_(max) ^(film) 3.0, 3.5, 5.85, 6.9,7.15, 8.2, 10.4 μ. NMR: δ 5.61 (s, 3, OH), 5.52 (s, 4, olefinic), 4.10(m, 2, 9 and 15-H), 0.91 (d, J=4.5, 11-methyl) ppm. Mass spectrum: M⁺ atm/e 352 (theory 352), M⁺ -H₂ O at m/e 334.2564 (theory 334.2507).

EXAMPLE 68 7-8α-Cyano-7β-((3S)-3-Hydroxy-Trans-1-Octenyl)-1,4-Dioxaspiro4.4!Non-6α-Yl!-Cis-5-Heptenoic Acid

A solution of 10.0 g. of 7-8-cyano-7-((3S)-3-hydroxytrans-1-octenyl)-1,4-dioxaspiro4.4!non-6.alpha.-yl!-cis-5-heptenoic acid and 13.0 g. ofpotassium-t-butoxide in 700 ml. of t-butanol was stirred at 25° undernitrogen for 40 hours. The reaction mixture was diluted with water,acidified with acetic acid and extracted with ether. After washing anddrying, the extract was evaporated and the residue chromatographed onsilica. Elution with 35% ethyl acetate in hexane followed byrecrystallization from ether-pentane gave 3.0 g. of the title product,m.p. 58.5°-61° C., λ_(max) ^(KBr), 3.0, 3.4, 5.8, 8.5, 8.9, 9.65, 10.3μ. NMR⁺ : δ 6.72 (S, 2, OH), 5.65 (M, 2, 13 and 14-H), 5.40 (M, 2, 5 and6-H), 4.18 (M, 1, 15-H), 3.92 (S, 4, ketal) ppm. Mass spectrum: M⁺ atm/e 405.2492 (theory 405.2514).

EXAMPLE 69 7-3α-Cyano-2-((3S)-3-Hydroxy-Trans-1-Octenyl)-5-Oxo-1α-Cyclopentyl!-Cis-5-HeptenoicAcid

An ice-cooled solution of 0.5 g. of 7-8α-cyano-7((3S)-3-hydroxy-trans-1-octenyl)-1,4-dioxaspiro4.4!non-6α-yl!-cis-5-heptenoic acid in 50 ml. of tetrahydrofuran wastreated with 12.5 ml. of hydrochloric acid and stirred at 0° C. for 1hour. The mixture was diluted with water, extracted with ether and theextract washed, dried and evaporated. Silica chromatography of theresulting residue was 35% ethyl acetate in hexane followed byrecrystallization from ether-hexane gave 0.26 g. of the title product,m.p. 71°-73° C., λ_(max) ^(KBr) 3.0, 3.4, 5.7, 7.9, 8.55, 9.8, 10.3 μ.NMR: δ 7.0 (S, 2, OH), 5.82 (M, 2, 13 and 14-H), 5.50 (M, 2, 5 and 6-H),4.28 (M, 1, 15-H), ppm. Calcd. for C₂₁ H₃₁ O₄ N: C, 69.77; H, 8.63; N,3.86. Found: C, 69.69; H, 8.83; N, 3.62.

EXAMPLE 70 3α-Cyano-2β- (3S)-3-Hyroxyoctyl!-5-Oxo-1α-CyclopentaneHeptonic Acid

A solution of 0.48 g. of 7-3α-cyano-2-((3S)-3-hydroxytrans-1-octenyl)-5-oxo-1α-cyclopentyl!-cis-5-heptenoicacid in 20 ml. of ethyl acetate was added to a prehydrogenatedsuspension of 0.22 g. of 5% Pd/C in 20 ml of ethyl acetate andhydrogenated at 25° C. and atmospheric pressure until 2 equivalents ofhydrogen were absorbed. The reaction mixture was filtered, evaporatedand chromatographed on 20% silver nitrated-silica. Elution with 50%ethyl acetate in hexane gave 0.164 g. of the title product, λ_(max)^(film) 3.45 (shoulder), 3.4, 4.45, 5.75, 6.85, 7.1, 8.65 μ. NMR: δ 3.60(M, 1, 15-H), 5.70 (S, 2, OH, removed with D₂ O) ppm. Mass spectrum: M+at m/e 365.2566 (theory 365.2566).

The subject matter which the applicants regard as their invention isparticularly pointed out and distinctly claimed as follows:
 1. Acompound of the formula: ##STR11## wherein R₂ is hydrogen, acetoxy andtetrahydropyranyloxy and R₃ is hydrogen or lower alkyl.
 2. The compoundaccording to claim 1, 7-3-cyano-2-(3-hydroxy-1-octenyl)-5-oxocyclopentyl!-5-heptenoic acid.